Wu Yupeng, Wang Yadong, Liu Ming, Nie Min, Wang Ying, Deng Yexuan, Yao Bing, Gui Tao, Li Xinyu, Ma Lingling, Guo Chan, Ma Chi, Ju Junyi, Zhao Quan
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210023, P.R. China.
Anhui Research Institute for Family Planning, Anhui Research Center for Population and Birth Control, Hefei, Anhui 230031, P.R. China.
Oncol Lett. 2018 May;15(5):6123-6130. doi: 10.3892/ol.2018.8092. Epub 2018 Feb 21.
Methylation of histone H4 lysine 20 (H4K20) has been associated with cancer. However, the functions of the histone methyltransferases that trigger histone H4K20 methylation in cancers, including suppressor of variegation 4-20 homolog 1 (Suv4-20h1), remain elusive. In the present study, it was demonstrated that the knockdown of the histone H4K20 methyltransferase Suv4-20h1 resulted in growth inhibition in chronic myeloid leukemia K562 cells. Disruption of Suv4-20h1 expression induced G arrest in the cell cycle and increased expression levels of cyclin dependent kinase inhibitor 1A (p21), an essential cell cycle protein involved in checkpoint regulation. Chromatin immunoprecipitation analysis demonstrated that Suv4-20h1 directly binds to the promoter of the p21 gene and that methylation of histone H4K20 correlates with repression of p21 expression. Thus, these data suggest that Suv4-20h1 is important for the regulation of the cell cycle in K562 cells and may be a potential therapeutic target for leukemia.
组蛋白H4赖氨酸20（H4K20）的甲基化与癌症相关。然而，在癌症中引发组蛋白H4K20甲基化的组蛋白甲基转移酶的功能，包括异染色质蛋白4-20同源物1（Suv4-20h1），仍不清楚。在本研究中，已证明组蛋白H4K20甲基转移酶Suv4-20h1的敲低导致慢性髓性白血病K562细胞生长受到抑制。Suv4-20h1表达的破坏诱导细胞周期中的G期停滞，并增加细胞周期蛋白依赖性激酶抑制剂1A（p21）的表达水平，p21是参与检查点调节的一种重要细胞周期蛋白。染色质免疫沉淀分析表明，Suv4-20h1直接结合p21基因的启动子，并且组蛋白H4K20的甲基化与p21表达的抑制相关。因此，这些数据表明Suv4-20h1对K562细胞中的细胞周期调节很重要，并且可能是白血病的潜在治疗靶点。
